O26 More than meets the eye … When inflammation extends beyond the anterior chamber

Abstract Case report - Introduction The differential diagnosis of paediatric uveitis is extensive. Classification starts by determining infectious versus non-infectious causes, anatomic location and associated intra-ocular and extra-ocular features. A relatively common referral to Paediatric Rheumatology from our Ophthalmology colleagues is of a child with a diagnosis of uveitis. This case highlights the importance and benefits of multidisciplinary team working across our regional network when caring for children with complex and rare conditions. Case report - Case description An 8-year-old-girl was referred by her local ophthalmology team to the paediatric rheumatology clinic with a diagnosis of pars-planitis. She had presented to them with blurred-vision and eye-“floaters”. On review, the girl reported that she had a 4-month-history of headaches and blurred-vision, associated with dizziness. She denied any eye-pain. Corresponding to the onset of her symptoms, she had suffered with Chickenpox. Her mother felt that she had "not been right since then". She noted that she was generally quieter and more fatigued than normal. Over the course of the 4 months, she was noted to have become clumsier and was bumping into things on a regular basis. She reported increasing visual difficulties in her right eye and initially attended for an optician review. The optician was concerned and referred for urgent ophthalmology opinion. She was diagnosed with bilateral pars-planitis, commenced on oral prednisolone and referred for paediatric rheumatology and tertiary ophthalmology assessment. The headaches improved following commencement on steroids. Positive findings on systems review included occasional oral ulcers, 1—2 times-per-month. They started about 1-month prior to the onset of her chickenpox and continued for the following 3—4 months. She denied any history of genital-ulcers or skin-rash. She had new-onset muscle soreness and tiredness after activity. She also described non-specific abdominal pain since having chickenpox, but no associated change in bowel habit. Examination revealed normal skin, hair, nail and joint examination. She had a soft systolic murmur (echocardiogram normal). She had RUQ tenderness on abdominal palpation (abdominal-USS – spleen upper limit of normal. Nil else). Relevant blood and stool samples were sent as part of a uveitis work-up panel. The paediatric ophthalmologist found right-intermediate uveitis with vitreitis and peripheral retinal changes in keeping with a peripheral exudative detachment. Similar changes were seen in the peripheral retina of the left eye. The impression was of bilateral pan-uveitis with retinal involvement. A subsequent oral fluorescein angiogram showed a widespread retinal vasculitis with some occlusive changes in the right-eye, and a tuft of retinal vascular leakage at the 5-o'clock position in the left eye. Case report - Discussion The differential diagnosis for paediatric retinal vasculitis is broad. It includes collagen vascular disorders, Behçet's disease, Eales’ disease, post viral or post vaccination, acquired toxoplasmosis, multiple sclerosis, systemic immunosuppression and Henoch-Schönlein purpura. The ANA, ENAs, dsDNA, ANCA, ACE, Toxoplasma and Lyme serology were all negative for this little girl. Her inflammatory markers were also normal. She was not on any regular medications prior to her illness and had not had any recent vaccinations. She had no significant past medical or family history of note. However, the onset of her symptoms did correspond to her having chickenpox. She was subsequently found to be positive for HLA B51. In view of the ophthalmology findings and positive HLA B51, the little girl was admitted for an urgent MRI/MRI to exclude neuro- Behçets. This was reported as normal. She was treated with a three-day pulse of IV methylprednisolone and discharged on oral prednisolone 10mg OD (weight 33.4kg). At present Bechet’s retinal vasculitis remains high in the list of differentials for this little girl; however, currently she does not strictly meet the diagnostic criteria for Bechet’s disease. She has been commenced on a steroid sparing agent, azathioprine. Her follow-up plan is to be reviewed in the joint paediatric rheumatology and ophthalmology clinic in 1 months’ time. Case report - Key learning points Retinal vasculitis may occur secondary to a systemic disease or an infectious agent, or as an isolated retinal aetiology. Given that the differentials are vast, a detailed history and examination are important to identify signs and symptoms of systemic disease. Appropriate investigations should be chosen to help narrow the differentials and ensure pathology that could lead to significant morbidity and mortality is not missed. With a case such as this, close collaboration between the paediatric ophthalmologist and rheumatologist is paramount to ensure the best outcome for the patient. With regards to treatment, small case series have described a refractory nature of retinal vasculitis in paediatric patients. One study report that almost 80% of patients with paediatric idiopathic uveitis show manifestations of retinal vasculitis, which is associated with a lower probability of inflammation control resulting in a worse visual prognosis. Points for discussion Thoughts on differential diagnosis? Thoughts on appropriate treatment when no definitive cause identified. Should we follow the National Behcet’s Disease pathway? Expected prognosis for paediatric retinal vasculitis?

cellulitis. Within a few days this lesion became necrotic and rapidly spread. At this point, he was transferred to a tertiary rheumatology centre. Within days to weeks, he developed several necrotic lesions affecting his trunk and limbs, with facial sparing noted. Approximately 30-35% of his whole-body surface became involved. He soon developed an oxygen requirement, with CTPA demonstrating lymphocytic interstitial pneumonitis without evidence of pulmonary emboli (PE). Throughout his admission, he had several other pathologies such as hyponatraemia that required level 2 care and severe noninfectious diarrhoea. Skin biopsy identified thrombotic vasculopathy. Serology confirmed triple positive antiphospholipid antibody status and a dsDNA titre of > 400 iU/mL. This was the first-time serology had been undertaken despite a history of three deep vein thrombosis (DVT) episodes and two PE incidents. He had no history of SLE symptoms. His initial management for vasculitis secondary to APLS at the point of limited necrosis consisted of IV methylprednisolone followed by rituximab and PO prednisolone. While there was some delay in the progression of his disease, new areas of necrosis arose, leading to the patient receiving cyclophosphamide. Low molecular weight heparin was used for anticoagulation. This gentleman later developed proteinuria and neurological symptoms, fulfilling the criteria for catastrophic antiphospholipid syndrome. He received plasma exchange, without an improvement. He developed complications from his disease and treatment, including poor wound healing. It became apparent his condition would not improve and active treatments were stopped. He passed away 6 weeks after initial presentation. Prior to his admission to hospital, his warfarin was swapped to a NOAC. This is thought to have been the trigger behind catastrophic thrombosis. Case report -Discussion: After excluding other conditions such as necrotising fasciitis, this gentleman was rapidly started on IV methylprednisolone to halt any further progression. This is because glucocorticoids have the greatest evidence base for managing this poorly understood acute disease manifestation. After this failed to manage his condition, he was given a further immunosuppressive agent in the form of rituximab. This was used after his serology confirmed triple antibody status. It was hoped this would stop any further immunological mediated disease progression. Oral prednisolone was started at 40 mg at this stage and kept under review with a tapering schedule. Cyclophosphamide was given within a few days of rituximab, with hope of a quicker onset of action. A careful MDT decision was made on these drug choices, particularly regarding their combined use and appreciating their side effect profiles. Cyclophosphamide has evidence behind its use, especially for those with APLS associated with lupus. While he did not develop any infections related to treatment, his condition progressed. Case reports suggest that plasma exchange can be useful in the management of catastrophic antiphospholipid syndrome, so the team recommended this. Consent at this stage became tricky due to his altered mental status, but it was felt he did demonstrate capacity for this specific decision. As his condition did not improve after this level of immunosuppression, the team reached the decision that no other treatments would likely change the outcome. He remained on oral steroids for the remainder of his admission. The other management facet of APLS crises pertains to anticoagulation. Low molecular weight heparin was recommended by the haematologists. His NOAC was stopped after the diagnosis was confirmed. Warfarin was restarted later in his admission given he had been well on this for years. Case report -Key learning points: This fascinating case exemplifies the importance of completing an antiphospholipid antibody screen for patients who present with unprovoked venous thromboembolic disease. NOACs are commonly used anticoagulant medications. Several case reports have demonstrated that patients with antiphospholipid syndrome experience breakthrough thromboembolic events when treated with NOACs. The highest risk is associated with history of arterial thrombosis and those with triple positive antibody status. Three clinical trials have either been completed or are in the process of investigating whether NOACs sufficiently prevent thromboembolic disease in these patients. The TRAPS study compared rivaroxaban to warfarin in those with triple antibody positive antiphospholipid syndrome. The study was terminated early given that higher adverse events were observed in the rivaroxaban arm (19%, n ¼ 11/59) versus warfarinised patients (3%, n ¼ 2/61). The RAPS study found no difference in thromboembolic risk and results from the ASTRO-APS study looking into apixaban are awaited. There is insufficient evidence to suggest that NOACs prevent VTE in a similar fashion to warfarin, so many still advocate the use of warfarin. The optimal immune management of this acute complication is not well elucidated, with a shortfall in mechanistic pathological understanding. The conference will generate discussion on this subject matter in detail. During the COVID-19 pandemic, it has been observed for patients to change anticoagulation from warfarin to NOACs. Given NOACs do not require monitoring, this medication change reduces the number of interactions patients have with healthcare services. We postulate this change triggered the crisis in our patient, where we suggest continuation of warfarin would have been ideal. This is due to the history of several unprovoked thromboembolic events without a prior antiphospholipid screen being completed. Dissemination of learning points from this case are imperative to ensure decision-making encompasses patients who may have undiagnosed antiphospholipid syndrome. Case report -Introduction: The differential diagnosis of paediatric uveitis is extensive. Classification starts by determining infectious versus non-infectious causes, anatomic location and associated intraocular and extra-ocular features. A relatively common referral to Paediatric Rheumatology from our Ophthalmology colleagues is of a child with a diagnosis of uveitis. This case highlights the importance and benefits of multidisciplinary team working across our regional network when caring for children with complex and rare conditions. Case report -Case description: An 8-year-old-girl was referred by her local ophthalmology team to the paediatric rheumatology clinic with a diagnosis of pars-planitis. She had presented to them with blurred-vision and eye-"floaters". On review, the girl reported that she had a 4-month-history of headaches and blurred-vision, associated with dizziness. She denied any eye-pain. Corresponding to the onset of her symptoms, she had suffered with Chickenpox. Her mother felt that she had "not been right since then". She noted that she was generally quieter and more fatigued than normal. Over the course of the 4 months, she was noted to have become clumsier and was bumping into things on a regular basis. She reported increasing visual difficulties in her right eye and initially attended for an optician review. The optician was concerned and referred for urgent ophthalmology opinion. She was diagnosed with bilateral pars-planitis, commenced on oral prednisolone and referred for paediatric rheumatology and tertiary ophthalmology assessment. The headaches improved following commencement on steroids. Positive findings on systems review included occasional oral ulcers, 1-2 times-per-month. They started about 1-month prior to the onset of her chickenpox and continued for the following 3-4 months. She denied any history of genital-ulcers or skin-rash. She had new-onset muscle soreness and tiredness after activity. She also described nonspecific abdominal pain since having chickenpox, but no associated change in bowel habit. Examination revealed normal skin, hair, nail and joint examination. She had a soft systolic murmur (echocardiogram normal). She had RUQ tenderness on abdominal palpation (abdominal-USS -spleen upper limit of normal. Nil else). Relevant blood and stool samples were sent as part of a uveitis work-up panel. The paediatric ophthalmologist found right-intermediate uveitis with vitreitis and peripheral retinal changes in keeping with a peripheral exudative detachment. Similar changes were seen in the peripheral retina of the left eye. The impression was of bilateral pan-uveitis with retinal involvement. A subsequent oral fluorescein angiogram showed a widespread retinal vasculitis with some occlusive changes in the right-eye, and a tuft of retinal vascular leakage at the 5-o'clock position in the left eye. Case report -Discussion: The differential diagnosis for paediatric retinal vasculitis is broad. It includes collagen vascular disorders, Behc¸et's disease, Eales' disease, post viral or post vaccination, acquired toxoplasmosis, multiple sclerosis, systemic i16 https://academic.oup.com/rheumap immunosuppression and Henoch-Schö nlein purpura. The ANA, ENAs, dsDNA, ANCA, ACE, Toxoplasma and Lyme serology were all negative for this little girl. Her inflammatory markers were also normal. She was not on any regular medications prior to her illness and had not had any recent vaccinations. She had no significant past medical or family history of note. However, the onset of her symptoms did correspond to her having chickenpox. She was subsequently found to be positive for HLA B51.

THE EYE IN RHEUMATIC
In view of the ophthalmology findings and positive HLA B51, the little girl was admitted for an urgent MRI/MRI to exclude neuro-Behc¸ets. This was reported as normal. She was treated with a three-day pulse of IV methylprednisolone and discharged on oral prednisolone 10mg OD (weight 33.4kg). At present Bechet's retinal vasculitis remains high in the list of differentials for this little girl; however, currently she does not strictly meet the diagnostic criteria for Bechet's disease. She has been commenced on a steroid sparing agent, azathioprine. Her follow-up plan is to be reviewed in the joint paediatric rheumatology and ophthalmology clinic in 1 months' time.
Case report -Key learning points: Retinal vasculitis may occur secondary to a systemic disease or an infectious agent, or as an isolated retinal aetiology. Given that the differentials are vast, a detailed history and examination are important to identify signs and symptoms of systemic disease. Appropriate investigations should be chosen to help narrow the differentials and ensure pathology that could lead to significant morbidity and mortality is not missed.
With a case such as this, close collaboration between the paediatric ophthalmologist and rheumatologist is paramount to ensure the best outcome for the patient. With regards to treatment, small case series have described a refractory nature of retinal vasculitis in paediatric patients. One study report that almost 80% of patients with paediatric idiopathic uveitis show manifestations of retinal vasculitis, which is associated with a lower probability of inflammation control resulting in a worse visual prognosis.
Points for discussion: . Thoughts on differential diagnosis? . Case report -Introduction: Uveitis is the most common extra-articular manifestation in axial spondyloarthritis (axSpa) and can affect up to a third of patients. It usually presents acutely and unilaterally in the anterior aspect as iritis. It is treated with topical steroids, mydriatics and immunosuppresants. Anti-TNF has been used successfully to treat uveitis in the context of axSpa and is the cornerstone of long-term control of recurrent uveitis. In severe cases, surgery in the form of vitrectomy is done. In axSpa patients who have failure or adverse effects from anti-TNF, alternative treatments are required to prevent the complications of recurrent uveitis and visual loss. Case report -Case description: A 68-year-old female patient with axSpA presented with recurrent anterior uveitis in the left eye. She had radiographic axSpA (ankylosing spondylitis) for 6 years and was HLA-B27 positive. Her past medical history included hypertension which was treated with amlodipine and ramipril. She was treated with adalimumab for 3 months for her axSpa and this was stopped due to intolerance. She was then switch to etanercept which controlled her axial and peripheral joints symptoms but she developed recurrent anterior uveitis. She remained on etanercept for 2 years. The uveitis was treated with Maxidex, dorzolamide and brimonidine eye drops. Despite this, her uveitis progressed and closed angle glaucoma and cataract. She was then switched to golimumab in order to gain control of her uveitis. She developed cutaneous vasculitis after starting treatment. She presented with a widespread vasculitic rash over her calves with areas of central necrosis. Her investigations revealed a WCC 15.04, plts 456, neut 9.17, eosin 0.30, ESR 84, CRP 45, U&E normal, ALP 178, ALT 36. Urine dip was negative for protein/blood/leuc/nitrites. Chest X-ray showed mild bronchial wall thickening in the right lower zone with a few ill-defined small opacites of indeterminate significance. Blood cultures x3 were negative. Echocardiogram was normal with no vegetations. CT thorax was normal. ANA 1:160, ENA negative, RF/anti-CCP negative, ANCA negative, C3 1.88, C4 0.38. She was commenced on prednisolone 20mg once a day weaning regime once infection was excluded. Her anti-TNF golimumab was stopped. She made a dramatic improvement in her cutaneous vasculitis after withdrawal of anti-TNF but developed attacks of uveitis in the left eye. This was treated trabeculectomy, intravitreal injection of Ozurdex and a YAG capsulotomy. She was commenced on secukinumab to treat her active axSpa and this has stabilised her uveitis. Case report -Discussion: Anti-TNF biologic drugs are effective in treating axial, peripheral joint as well as extra-articular manifestations (EAMs) in axSpa. Uveitis is the commonest EAM in axSpa and responds very well to anti-TNF drugs. The presence of HLA-B27 positivity as in our case, predisposes the patient to uveitis and EAMs. Uveitis may lead to complications such as glaucoma, cataracts, cystoid macular oedema, detached retina and posterior synechiae. In our case, the patient had the first three complications as a result of recurrent uveitis and withdrawal of anti-TNF due to adverse events. She required surgery include trabeculectomy, intra-vitreal injection and capusulotomy. Ongoing systemic treatment is required in her to avoid any further loss of vision. In a third of axSpa patients there may be failure or adverse reaction to anti-TNF. In patients who have failed anti-TNF they may be switched to another anti-TNF such as in our case. In patients with adverse reactions to anti-TNF, the choice is to either re-challenge with anti-TNF or switch to another drug with a different mode of action. For axSpa, the options include anti-IL17 and JAK inhibitors. Adverse reactions to anti-TNF include cutaneous manifestations such as cutaneous vasculitis as in our case, cutaneous lupus, psoriasis, hidradenitis suppurativa, lichen planus, vitiligo and alopecia areata. Having stopped anti-TNF due to the cutaneous vasculitis, we switched her to secukinumab for control of her axSpa. This also resulted in improved control of her uveitis with reduced frequency and severity of uveitis. In three phase 3 RCTs (SHIELD, INSURE, ENDURE) aiming to determine efficacy of secukinumab in non-infectious uveitis (Behcet's and non-Behcet's) against placebo, there was no significant differences in uveitis recurrence between secukinumab treatment groups and placebo groups in any study (primary end-point). More studies are required to assess the efficacy of IL-17 inhibitors in treating and preventing uveitis in axSpa.
Case report -Key learning points: Uveitis is the most common extra-articular manifestation (EAM) in axSpa. Early assessment and treatment are required to prevent complications such as visual loss. Close liaison and working with ophthalmologists is essential in order to improve patient outcome in axSpa. In severe cases of uveitis with complications, surgery may be required to prevent visual loss. Anti-TNF drugs are very effective in treating axSpa and are also beneficial in treating uveitis. A third of axSpa patients may have failure or adverse reaction to anti-TNF. The adverse event may include cutaneous manifestations such as vasculitis. This may necessitate withdrawal of anti-TNF. In patients who are not able to take anti-TNF, suitable alternatives such as anti-IL-17 and JAK inhibitors are used to treat axSpa. The impact of anti-IL17 and JAK inhibitors on uveitis in axSpa is yet to be determined. In our case, anti-IL17 secukinumab was shown to be effective in reducing the recurrence of uveitis. This requires further research to study its efficacy in treating and preventing uveitis in axSpa.

Mithun Chakravorty, Archana Pradeep and Ira Pande Nottingham University Hospital, Nottingham, United Kingdom
Case report -Introduction: Relapsing polychondritis (RP) is a rare autoimmune disorder characterised by inflammation of cartilaginous structures throughout the body. It usually presents in the fourth and sixth decade, and commonly affected areas include the nasal and respiratory tracts, external ears and joints. Ocular involvement is reported in around 65% of RP patients during their lifetime but is rarely sightthreatening. However, we present an unusual case of recurrent ocular inflammation due to RP that resulted in unilateral posterior scleritis with sub-retinal exudation, and posed a high risk of retinal detachment. Prompt escalation of immunosuppressive treatment was required to prevent this. Case report -Case description: A 48-year-old man of south-east Asian descent presented to rheumatology in December 2020 with a typical history of new inflammatory arthritis of 4 weeks duration. He was known to have bilateral episcleritis and ocular hypertension for 3 years and took Brinzolamide and Latanoprost eye drops, as well as